Polarized inert noble gases can produce improved NMR signals in and/or MRI images of certain areas and regions of the body. Noble gases, such as polarized helium-3 (“3He”) and xenon-129 (“129Xe”), have been found to be particularly suited for this purpose. Unfortunately, the polarized state of the gases is sensitive to handling and environmental conditions and can, undesirably, decay from the polarized state relatively quickly.
Hyperpolarizers are used to produce and accumulate polarized noble gases. Hyperpolarizers artificially enhance the polarization of certain noble gas nuclei (such as 129Xe or 3He) over the natural or equilibrium levels, i.e., the Boltzmann polarization. Such an increase is desirable because it enhances and increases the MRI signal intensity, allowing physicians to obtain better images of the substance in the body. See U.S. Pat. Nos. 5,545,396; 5,642,625; 5,809,801; 6,079,213, and 6,295,834; the disclosures of these patents are hereby incorporated by reference herein as if recited in full herein.
In order to produce the hyperpolarized gas, the noble gas can be blended with optically pumped alkali metal vapors such as rubidium (“Rb”). These optically pumped metal vapors collide with the nuclei of the noble gas and hyperpolarize the noble gas through a phenomenon known as “spin-exchange.” The “optical pumping” of the alkali metal vapor is produced by irradiating the alkali-metal vapor with circularly polarized light at the wavelength of the first principal resonance for the alkali metal (e.g., 795 nm for Rb). Generally stated, the ground state atoms become excited, then subsequently decay back to the ground state. Under a modest magnetic field (10 Gauss), the cycling of atoms between the ground and excited states can yield nearly 100% polarization of the atoms in a few microseconds. This polarization is generally carried by the lone valence electron characteristics of the alkali metal. In the presence of non-zero nuclear spin noble gases, the alkali-metal vapor atoms can collide with the noble gas atoms in a manner in which the polarization of the valence electrons is transferred to the noble-gas nuclei through a mutual spin flip “spin-exchange.” Alternative polarization enhancement techniques may also be used.
After the polarization process, the hyperpolarized gas is typically separated from the alkali metal (where spin-exchange techniques have been employed) prior to administration to a patient to form a non-toxic pharmaceutically acceptable product. Unfortunately, during production and/or during and after collection, the hyperpolarized gas can deteriorate or decay relatively quickly (lose its hyperpolarized state) and therefore must be handled, collected, transported, and stored carefully.
In the past, several researchers have used hyperpolarized gas compatible ventilators for delivering polarized gas to subjects to image hyperpolarized noble gases such as helium and xenon. For example, Hedlund et al., in MR-compatible ventilator for small animals; computer controlled ventilation for proton and noble gas imaging, 18 Magnetic Resonance Imaging, pp. 753-759 (2000), state that ventilators have been in routine use in their laboratory for a number of years. See also, Hedlund et al., Three-dimensional MR microscopy of pulmonary dynamics, Society of Magnetic Resonance (New York, N.Y., 1996); and a poster presented by Hedlund et al. at the Amer. Thoracic Society 1998 International Meeting (Chicago, 1998), entitled MRI of pulmonary airways with hyperpolarized helium; a computer-controlled ventilator for imaging synchronous gas delivery in animal studies (describing ventilator technology). In addition, Black and co-workers have used a hyperpolarized gas-compatible ventilator to generate what is believed to be the first ever in vivo images of hyperpolarized 3He in guinea pig lungs. See Black et al., In vivo He-3 MR images of guinea pig lungs, Radiology, 199(3), pp. 867-870 (1996). One known commercial small animal ventilator that may have been modified to dispense hyperpolarized gas and other respiratory gases have been is believed to be available from CWE Inc. (Ardmore, Pa.) as Model SAR-830.
Unfortunately, conventional small animal ventilators used to deliver hyperpolarized gases do not provide a way to accurately determine the volume delivered to the animal. Generally stated, conventional ventilators cannot adequately determine the volume delivered to the animal lungs separate from the volume delivered by the system itself. For example, certain conventional ventilators have proposed using flow meters with pressure transducers that control inspiration pressure and calculate an estimated volume by averaging the flow output to the subject over time. The variability in such an estimate may be undesirable, particularly when the amount of delivered polarized gas is small and the MRI/NMR signal depends on the amount, concentration and polarization level of polarized gas delivered, such as is the case for polarized gas investigations of small animals using millimole concentration ranges.
Thus, there remains a need for systems that can more accurately determine the amount of a gas and/or number of moles of gas delivered to an animal's lungs.